Antiphospholipid syndrome is a general term for a group of diseases for which antiphospholipid antibodies are observed in blood and which present clinical symptoms such as arteriovenous thrombosis and recurrent abortion and fetal death. “Antiphospholipid antibodies” (aPL) is a general term for autoantibodies which bind to phospholipids or to complexes of phospholipids and proteins. There are various antibodies as aPL, and examples thereof are anti-cardiolipin antibodies, anti-β2 glycoprotein I antibodies, phosphatidylserine-dependent antiprothrombin antibodies, and lupus anticoagulants (LA).
LA is defined as “an immunoglobulin that inhibits phospholipid-dependent blood coagulation reactions without inhibiting individual coagulation factor activities”. LA is considered as an autoantibody that inhibits phospholipids in phospholipid-dependent coagulation reactions. On the other hand, although LA inhibits phospholipids necessary for phospholipid-dependent coagulation reactions, patients having LA show thrombotic symptoms.
Currently, LA screening tests utilize a method in which a reagent containing a low concentration of a phospholipid is used to facilitate phospholipid-inhibiting reaction caused by LA, thereby to confirm prolongation of clotting time. In such tests, a reagent for measuring activated partial thromboplastin time (APTT) is diluted to be used, or a reagent whose phospholipid concentration is set to be low in advance, such as in PTT-LA (registered trademark) (Roche Diagnostics), is used.
U.S. Patent Application Publication No. 2012/0052585 discloses a reagent kit that is specialized in detecting LA and that includes two types of reagents having different phospholipid concentrations. This reagent kit suppresses prolongation of clotting time caused by LA, thereby enabling a group of LA positive specimens to be clearly distinguished from a group of the other specimens. However, detection of LA by this reagent kit requires measurement of clotting time for each of the two types of reagents.
Conventional APTT measuring reagents used in screening tests do not have satisfactory sensitivities to LA. Therefore, with conventional reagents, even in mixing tests with normal plasma, it is difficult to clearly distinguish the group of LA positive specimens from the group of the other specimens. Thus, there is a demand for means that can improve sensitivity to LA and that can accurately distinguish the group of LA positive specimens from the group of the other specimens.